There are a number of intraruminal devices and sustained release capsules and formulations presently available. In general the devices currently available are in the form of a capsule, which comprises: a substantially hollow tubular body, which is sealed at one end by a cap, and partially sealed at the second end by an annular flange, which defines an opening. There is provision within the body for the inclusion of a solid therapeutic composition.
Many of the currently available intraruminal devices contain a spring and plunger mechanism for urging the solid therapeutic composition towards the opening. The cap end may also have attached to it a plurality of resilient arms designed to prevent regurgitation of the device by the animal.
Intraruminal devices are inserted through the oesophagus into the animal's rumen. Once in the rumen they commence the release of the therapeutic composition over a prolonged period of time. A number of such formulations are available which are all capable of releasing a single therapeutic drug, such as an anthelmintic, and in some cases a range of supplementary trace elements.
Sustained release capsules have been available for over fifteen years. These devices release active ingredients or trace elements into the rumen of an animal for a period of 90-180 days.
There are two main types of sustained released capsule:
Simple Erodible Systems
These were the first type of sustained release device introduced to the market. They are generally of a waxy or metallic construction and are in the shape of a simple cylinder. Erosion either occurs from over the entire surface of the device, or in some cases the device may have been dipped in a coating material so that only the ends of the device are exposed. In this case payout will be able to be controlled more effectively. The interaction with the rumen contents (amount of grass and liquid content) determines the rate of erosion of the device.
Examples of such devices include:
Alltrace Mineral Bolus (Agrimin, UK)—This is an erodible bolus containing: Copper (16,379 mg), Cobalt (236 mg), Selenium (251 mg), Manganese (8,326 mg), Zinc (13,382 mg), Iodine (497 mg), Vitamin A (549,408 i.u.), Vitamin D (3109,881 i.u.) and Vitamin E (1,099 i.u.). Two boluses are administered to each animal weighing 150 kgs or more, with the payout period being 240 days. To retain the bolus in the rumen the device has a sold metal densifier element which erodes after the lighter mineral elements have dissolved. The advantage of the device is the high loading of active ingredients and the fact that the device will fully erode leaving no part retained in the animal. Disadvantage of this style of erodible bolus is that it is not possible to achieve a linear release rate.Optimag Magnesium Bolus (Norbrook, UK)—A solid metallic bolus containing 100 g of magnesium released over approximately 4 weeks. These are used in adult cattle as an aid to maintenance of magnesium intake.
In both of the above cases the aim of bolus administration is to maintain mineral levels in the treated animal for a prolonged period of time. Neither device allows for complex payout profiles as might be required if the farmer wished to deliver an immediate short-acting dose of a particular active ingredient to be followed by the sustained payout of the minerals in question.
Sustained-Release Devices
A relatively new technology is the category of sustained-release devices. In general these are in the form of a plastic capsule, comprising: a substantially hollow tubular body, which is completely sealed at one end by a cap, and partially sealed at the second end by an annular flange, which defines an opening. There is provision within the body for the inclusion of a solid therapeutic composition.
Many of the currently available sustained release devices contain a spring and plunger mechanism for urging the solid therapeutic composition (either in the form of solid wax or stack of tablets) towards the opening. Other devices rely on osmotic pressure to expand a driver portion in the base of the capsule. This driver portion causes the active contents to be expelled from the open end of the capsule. The diameter of the opening can be used to increase or restrict the speed of payout of the device.
The capsule may be retained in the rumen of the animal either by a plurality of resilient arms protruding from the cap end of the device, or by a weighted metal densifier element within the body of the device.
Typically this style of device is used to deliver active ingredients requiring a greater precision of payout such as anthelmintics. In these cases the daily dose of anthelmintic is low compared to the amount recommended in a standard oral dose.
Examples of sustained release devices include:
IVOMEC SR Bolus (MSD Agvet)—Containing 1.72 g ivermectin releasing over 140 days. This device uses osmotic pressure to expand a driver portion in the base of the capsule. The expansion of this driver portion urges the solid wax formulation containing ivermectin towards the opening.EXTENDER SeCo (Merial)—Containing 4.62 g albendazole releasing over 100 days, and IVOMEC Maximizer Capsule (Merial)—Containing 160 mg ivermectin releasing over 100 days. Both of these devices utilise a spring portion to urge a stack of tablets containing the active ingredients towards the opening. At the opening the face of the exposed tablet forms a gel which is released into the rumen.
There are times however when even sustained release of one or more substances over a prolonged period is insufficient to satisfy animal health needs. In certain cases the farmer may wish to deliver an additional substance in an immediate or dump release fashion prior to or following the period of sustained release.
Examples of such cases could include:
When a secondary trace element or mineral treatment is required to be given to an animal at the same time as a sustained release treatment of an anthelmintic. Traditionally this would mean that the farmer would administer a separate treatment in the form of a liquid drench or oral capsule. An example of this is that farmers will often give a copper oxide needle treatment in the form of a gelatine capsule for preventing copper deficiency. It can be recognised that this separate treatment is time consuming and inconvenient.
A further example is that the manufacturers of EXTENDER SeCo recommend that a large “primer” or initial dose of an effective oral anthelmintic is given at the same time as the capsule is inserted into the animal. The purpose of this primer dose is to control the adult stage parasites that are resident in the animal. Once this is done the capsule will be able to effectively control any new incoming larvae for the effective payout period of the device.
Another example is that there is a concern that some single active sustained release anthelmintic devices may not effectively control all parasites for the full duration of the payout period. In some cases it may be desirable to administer to the animal what is known as an “exit” dose. This is a large dose of anthelmintic administered at a single time point sufficient to control adult parasites that may have survived the smaller sustained dose of anthelmintic.
Recently there have been attempts to incorporate priming and/or exit doses into sustained release capsules so that there is no need for the farmer to administer a separate treatment.
These are typically made by incorporating one or more fast releasing tablets into the stack of sustained release tablets contained within the device. These fast release tablets contain disintegrants and effervescent materials. Unfortunately the fast release of the tablet can allow moisture to seep through the annular flange defining the opening and down the inside of the capsule body. This can then impede release of subsequent sustained release tablets.